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This material is based upon work supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, and the Office of Military

Family Readiness Policy, U.S. Department of Defense under Award Number 2015-48770-24368.

Phytonutrients and Cardiovascular Disease

Connecting military family service providers

and Cooperative Extension professionals to research

and to each other through engaging online learning opportunities

militaryfamilies.extension.org

MFLN Intro

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Elvira de Mejia, MSc., Ph.D., C.F.S.

Professor and Assistant Dean for Research and University

Scholar at the University of Illinois.

She has published over 190 peer-reviewed scientific publications

and 25 chapters in books in the areas of Food Science and

Human Nutrition.

The long-range goal of her research program is to enhance the

health of individuals by the identification and evaluation of the

benefits of bioactive compounds in plant foods.

She is currently working on bioactive phytochemicals, mainly

proteins, peptides and flavonoids from legumes, cereals, herbs

and fruits and their effect on prevention of chronic diseases.

Today’s Presenter

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Learning objectives:

1. Explain the state of the art of the science behind the effect

of bioactive compounds in plant foods related to

cardiovascular disease.

2. Discuss the potential of fruit and vegetable flavonoids on

heart health implications and their capacity to protect

against chronic diseases.

3. Identify the sources of bioactive compounds in the diet and

educate clients/patients in selecting foods to reduce their

risk of cardiovascular disease.

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• Introduction• Inflammation and cardiovascular disease

• Risk factors for heart disease

• Bioactive compounds related to CVD

– Phenolic compounds and biological activity

– Absorption and metabolism of phenolic compounds

– Anthocyanins and risk of CVD

– Phytosterols and risk of CVD

– Proteins and peptides and risk of CVD

• Take-home message

Overview

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Belief in foods with Health Benefits

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Awareness of Food Component/Health Pairs

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Diet and cardiovascular disease

• Diet has a significant impact on the

development of heart disease

• Inflammation is directly involved in the

initiation and progression of atherosclerotic

lesions

• Several bioactive compounds inhibit

inflammation (intermediate risk CVD factor).

81Heron MP, et. al, Nat. Stat. Reports, 2009.

2de Mejia, EG., et al, Peptides, 30(12), 2009.8

Risk Factors for Heart DiseaseConditions

- High blood pressure*

- High cholesterol*

- Diabetes*

Behavioral

- Unhealthy diet*

- Physical inactivity

- Obesity*

- Too much alcohol*

- Tobacco use

Family History

- Genetics

- Becoming older

- Ethnicity SOURCE: Center for Disease Control and Prevention (CDC)* Diet Related and can be modified by behavioral changes

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Image via openclipart.org CC0

Inflammation and Atherosclerosis

Libby, P., Am. J. Clin. Nut., 2006

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What are the main components of the Mediterranean Diet?

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Key Components of Mediterranean Diet

The Mediterranean diet emphasizes:

• Eating primarily plant-based foods, such as fruits and vegetables,

whole grains, legumes and nuts

• Replacing butter with healthy fats such as olive oil and canola oil

• Using herbs and spices instead of salt to flavor foods

• Limiting red meat to no more than a few times a month

• Eating fish and poultry at least twice a week

• Enjoying meals with family and friends

• Drinking red wine in moderation (optional)

• Getting plenty of exercise

12 Diet/Benn/Flickr CC0Rickr/Flickr CC0 Lundback/Flickr CC0

The DASH DietDietary Approaches to Stop Hypertension

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The DASH diet includes:• Whole grains (6 to 8 servings a day)

• Vegetables (4 to 5 servings a day)

• Fruits (4 to 5 servings a day)

• Low-fat or fat-free milk and milk

products (2 to 3 servings a day)

• Lean meat, poultry, and fish (6 or

fewer servings a day)

• Nuts, seeds, and beans (4 to 5

servings a week)

• Healthy fats and oils (2 to 3 servings

a day)

• Sweets, preferably low-fat or fat-free (5

or fewer a week)

• Sodium (no more than 2,300 mg a day)

• If you drink alcohol, limit yourself to 2

drinks or less per day for men and 1

drink or less per day for women

• To reduce your blood pressure even

more, replace some DASH diet

carbohydrates with low-fat protein and

unsaturated fats

• For weight loss, reduce your daily

calories to 1,600 per day

• Lower your sodium to no more than

1,500 mg per day if you are age 40 or

older, are African American, or if you

have been diagnosed with high blood

pressure

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Questions

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Lignans,

Phytoestrogens &

phytosterols

Jamaica

(Hibiscus sabdariffa)

Anthocyanins

Nopal

(Opuntia ficus-indica)

Carbohydrates, phenols

Amaranth

(Amaranthus cruentus)

Proteins

Polyphenols

Bioactive phytochemicals in foods

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Chia

(Salvia Hispanica)

Omega-3 fatty acids

Pepper,

(Capsicum)

Capsaicin, carotenoids

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Saponins Isoflavones

Bioactive peptides Lunasin

Bowman Birk inhibitor

Amaranth

Amaranthus cruentus

Dried parsley

Celery seeds

Herbal Teas

Yerba Mate tea

Mexican oregano

Lippia graveolensHibiscus sabdariffa

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Putative beneficial biological effects

attributed to dietary bioactive compounds

Cam, A., Gonzalez de Mejia, E. 2011.

Role of dietary proteins and peptides

in cardiovascular disease. Molecular

Nutrition and Food Research.18

Increased intake of phenolics

and dietary flavonoids

Burton-Freeman 2010; Del Rio 2010;

Miguel 2011; Pan 2010.

Health benefits:

Decreased incidence of disease

Anti-inflammation:

Post-prandial, acute, chronic

Decrease cardiovascular

disease risk factors

Antioxidant Activity:

Scavenging free radicals,

reducing oxidative

stressAnti-cancer

properties

Improved diabetes tolerance

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Bioactive Compounds in Fruits and Vegetables

Curcumin

(Curcuminoid)

Flavonoids

Quercetin (Flavonol)

Limonoids

Limonin

EGCG (Flavanol) Genistein (Isoflavone)

Resveratrol

(Stilbenoid)

Apigenin (Flavone)

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Chemical diversity of polyphenolsSimple phenols are represented by (a) catechols and (b) stilbenes, and

polyphenols in (c) anthocyanins, (d) flavonols, (e) flavanols and (f) isoflavones

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Flavonoid Absorption and Metabolism

Ingestion Absorption Metabolism

Excreted in

urine bile or

feces

Foods

containing

naringenin

Small and

large

intestine

• Methylation

• Sulfation

• Glucuronidation

• Acetylation

Tissue

Absorption

Juice: 15 mg

Cmax = 0.25 μMCmax = 0.048 μg/L

Krogholm et al., (2010) Eur J Clin Nutr22

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Absorption and Metabolism of

Anthocyanins• Consumption among the highest of all flavonoids due to

their wide distribution in foods.

• Estimated daily intake of anthocyanins in the United States

is between 180-215 mg, may be as low as 12.5 mg per day.

• Absorption mainly in the small intestine and stomach.

• Very efficient epithelial tissue uptake.

• Gut microbiota cleave glycosidic linkages.

• Reach peak plasma concentrations quickly.

• 1-120 nM

• Less than 1% recovery in urine.

• Metabolites and degradation products may play a key role

in their biological activity.23

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Hibiscus sabdariffa shows scientific support demonstrated in in vitro,

preclinical and clinical models that its regular consumption may help to

control and prevent certain diseases, without health risk.

Chlorogenic acid

Protocatechuic

acid

Mojica, Li , Gonzalez de Mejia. Hibiscus sabdariffa L.: Phytochemical Composition and Nutraceutical Properties

In Hispanic Foods: Chemistry and Bioactive Compounds; ACS Symposium Series; American Chemical Society: 2012.

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McKay,Chen,Saltzman,Blumberg. J. Nutr.

140: 298–303, 2010.

A randomized, double-

blind, placebo-controlled

clinical trial, 65 pre- and

mildly hypertensive adults,

age 30–70 y, not taking

blood pressure (BP)-

medications, with either 3

240 mL servings/d of

brewed hibiscus tea or

placebo beverage for 6 wk.

A standardized method

was used to measure BP

at baseline and weekly

intervals.

• At 6 wk, hibiscus tea lowered

systolic BP (SBP) compared

with placebo (-7.2 +/- 11.4 vs. -

1.3 +/-10.0 mm Hg; P = 0.030).

• Participants with higher SBP at

baseline showed a greater

response to hibiscus treatment

(r = -0.421 for SBP change; P =

0.010).The dietary change

assessed, regularly

incorporating

3 servings/d of

hibiscus tea into the

diet, effectively

reduced BP in

pre- and mildly-

hypertensive adults

Hibiscus Sabdariffa L. Tea

(Tisane) Lowers Blood

Pressure in

Prehypertensive and Mildly

Hypertensive Adults.

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Anthocyanins: A colorful array of health promoting

properties

Anthocyanins in foods as modulators of

inflammatory pathways to prevent the

development of chronic diseases

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Best recognized for high content of flavonoids (anthocyanins)

and tannins [condensed tannins (proanthocyanidins)]

Health benefits:

Antioxidant activity, anti inflammatory effects,

cardiovascular protection anti-diabetic and anti-obesity

properties, inhibition of carcinogenesis

(Vaccinuim floribundum)

Berry spherical,

5-8 mm diam., blue-black.

Schreckinger, et al., 2010. Berries from South America: A Comprehensive Review on Chemistry, Health

Potential and Commercialization. J. Med. Food 13 (2): 233-246. 27

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Role of anthocyanins from berry beverages

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Phenolic compounds in fruits and vegetables,

specifically flavonoids reduce inflammation

LUTEOLIN

mg/100 g

APIGENIN

mg/100 g

Juniper berries 69 3

Vinespinach -- 62

Mexican oregano 1029 18

Kumquat -- 22

Celery heart 4 19

Parsley 1 215

Pimento peppers -- 10

Radicchio 48 --

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Summary of results for phenolic compounds and CVDRESVERATROL No reports on long-term health or survival in humans

CATECHOLS (curcumin) Non-significant effect of curcumin on lipid profile when considering

heterogeneous populations

Beer or Wine POLYPHENOLS Not strong evidence showing that consumption of beer or wine could help

to improve risk of CVD

ANTHOCYANINS B Not strong evidence supporting that anthocyanins help to decrease risk of

CVD and further studies are required

CATECHINS B No robust evidence to suggest a beneficial effect of tea catechins on

prevention of CVD

FLAVANOLS

(dark-chocolate) B

Efficacy of cocoa flavanols in BP and heart function improvement, studies

needed using flavanol-free controls

FLAVONOLS (quercetin) B Effective at reducing BP in hypertensive men, further analysis in greater

cohorts are needed.

ISOFLAVONES B Greater population sizes. Significant improvement in women with low

baseline Flow Mediated Dilation levels

PROANTHOCYANINS

C

Insufficient evidence to determine if extracts containing procyanidins could

improve CVD risk

Some polyphenols used as BC such as flavonols decrease risk factors of CVD. Need to develop

better quality long-term, crossover design, double-blinded, long term, placebo/controlled,

randomized clinical trials as well as elaborate rigorous meta-analysis.

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Phytosterols – A well known example of a

bioactive compound

• Plant origin compounds similar to the structure of cholesterol.

• Consumption in the diet ~200 – 400 mg/d.

• Minimally absorbed (<1%).

• Typical plasma levels 0.4 – 0.5 mg/dl.

• Act reducing the intestinal absorption of intestinal cholesterol (dietary and endogenous).

• The intake of 1-3 g/day can reduce total cholesterol ~10% and LDL-cholesterol in ~15%.

Efficacy of phytosterols in enriched foods has been confirmed by a meta-analysis of 84 controlled clinical studies.

Demonty et al., 2009. J. Nutr. 139: 271-84

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Blood Cholesterol and Mortality due

to Coronary Heart Disease

mg/dL

0

2

4

6

8

10

12

14

16

18

140 190 240 290

Blood Cholesterol

Source: MRFIT Study; adapted from JAMA 256, 1986.

A 1% decrease in blood cholesterol represents a 3% reduction in the risk of coronary heart disease.

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Phystosterols & Serum Cholesterol

Subject number 17 ± 3

Dose 13 ± 1.1 g/d

Duration 27 ± 4 wks

Cholesterol response -20 ± 1.5%

Averages for 52 studies: 1953-1980

Pollack & Kritchevsky, (1981) Sitosterol. Basel, S. Karger.

The efficacy of phytosterols-fortified foods has been confirmed in a recent meta-analysis of

84 clinical studies (Demonty et al. 2009, J. Nutr. 139:271)

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How Sterols Work in the Body

• Phytosterols are believed to interfere with:

– cholesterol incorporation into mixed micelles

and/or

– cholesterol absorption into cells of small

intestine

and/or

– cholesterol remaining in cells of small intestine

• Phytosterol consumption results in

decreased cholesterol absorption leading to

decreased serum cholesterol.

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Safety Considerations“Phytosterol is one of the most studied substances in regard

to safety”

• Phytosterols are minimally absorbed (<5%).

• Phytosterolemia is a rare genetic condition (1:5,000,000).

• Not mutagenic, not teratogenic.

• Blood levels of fat soluble vitamins are not affected.

• Decrease in blood carotenoid levels lacks clinical

significance and can be compensated by a diet rich in

fruit and vegetables.

• No convincing evidence of an association between

elevated levels of blood phytosterols and increased CHD

risk.

Phytosterols are considered safe.(U.S. FDA, EU-SCF, EFSA, FSANZ, JECFA (FAO/WHO), HC)

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U.S. Model Claim (FDA, 2000)Plant Sterol/Stanol Esters and Risk

of Coronary Heart Disease

Foods containing at least 0.65 g per serving

of vegetable oil sterol esters, eaten twice a

day with meals for a daily total intake of at

least 1.3 g, as part of a diet low in saturated

fat and cholesterol, may reduce the risk of

heart disease.

36

In 2016 FDA broadened the food categories for the

addition of phytosterols to:

• Margarines & Vegetable Oil Spreads

• Dressing for Salads

• Beverages

• Vegetarian Meat Analogs

• Dairy Analogs

• Fruit/Vegetable Juices

• Cheese and Cream

• Edible Vegetable Oils

• Baked Foods

• Adult Ready-to-Eat Breakfast Cereals

Source: FDA GRAS letter to ADM, GRN No. 000176

• Mayonnaise

• Pasta and Noodles

• Sauces

• Salty Snacks

• Process Soups

• Puddings

• Yogurt

• Adult Confections

• Snack Bars

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Soy Protein

• Soybean possesses biologically active peptides

• 1999 FDA claim: “25 g of soy protein per day as part

of a diet low in saturated fat and cholesterol, may

reduce the risk of heart disease.”

• New studies specifically implicate chronic

inflammation as a major contributor to the

progression of atherosclerosis

• Necessitates determination of mechanism of action

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Physiological Functions of

Bioactive Peptides

Anti-cancer

Immunomodulatory

Antimicrobial

Anti-obesity

3939

Opioid

Antioxidant

Hypocholesterolemic

Anti-inflammatory

Lipkin y col., 2005; Torruco-Uco y col., 2008; Silva-Sánchez y col., 2008; Tironi y Añón, 2010

Bioactive Peptides

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500 ml /day

3 months

Low Glycinin Soymilk (LGS) n=19

12 g protein/day (49.5% β-conglycinin), 1% fat, 200 Kcal

Conventional Soymilk (S) n=2312 g protein/day (26.5% β-conglycinin), 1% fat, 200 Kcal

Bovine milk (M) n=22

12 g protein/day (0% β-conglycinin), 1% fat, 200 Kcal

IRB # 09454

SUBJECT ELIGIBILITY

Male (age:18-45). BMI>25, less than 300 lb. Non smoker, non vegetarian, non athletes,

free of chronic diseases.

WASHOUT PERIOD

(1 week) - Soy free diet

64 subjects

scattered

Soymilk

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LGS consumption decreased serum

oxidized LDL after 3 months

-45

-35

-25

-15

-5

5

15

25

LGS S M

Re

lati

ve d

iffe

ren

ce (

%)

b b

a

S vs. M (p = 0.014)LGS vs. M (p = 0.025)

Plasma interleukin-6 decreased after 3

months of LGS and S consumption

Adiponectin increased after 3 months

of LGS consumption

All values expressed as means ± SEM

**Change affected by age (p = 0.03) and initial BMI (p = 0.02)

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Soymilk increased serum antioxidant capacity after

3 months of consumption

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-40

-30

-20

-10

0

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20

30

40

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LGS S M

Re

lati

ve d

iffe

ren

ce (

%)

Treatments

LGS vs. M (p = 0.001)

S vs. M (p < 0.001)

b

aa

means ± SEM

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Pathogenesis of CVD

• Diet has a significant impact on

hypertension, obesity and diabetes,

which are major risk factors for the

development of CVD, specifically

atherosclerosis (Roger et al., 2012).

• Initiation and progression of

atherosclerosis is influenced

extensively by inflammation (Moore et al., 2011).

• Certain proteins and peptides can

regulate atherosclerotic lesions (Antonov et al., 2010; Gauze, 2010).

Xiong, et al., 2009

NIH, https://www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis

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The build-up of plaque over time causes

____________________which can lead

to serious problems, including heart

attack, stroke, or even death.

What is the main treatment for

atherosclerosis?

Plaque is made up of fat, cholesterol, calcium, and other

substances found in the blood. Over time, plaque hardens

and narrows your arteries. This limits the flow of oxygen-rich

blood to your organs and other parts of your body.

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Questions

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Take-home message

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2015-2020 Dietary Guidelines

Follow a healthy eating pattern (at appropriate calorie level)

• A variety of vegetables-dark-green, red, and orange; legumes,

starchy and other – Fruits, especially whole fruits

– Grains, at least half whole grains

– Fat-free or low-fat dairy

– Protein foods, including seafood, lean meats, poultry, eggs, legumes, nuts, seeds and soy

products

– Oils

Limit:

• Saturated fat and trans-fat

• Added sugar

• Sodium

Source: Adapted from ODPHP, HHS/USDA, 2015

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American Heart Association Dietary

Recommendations

Eat a variety of nutritious foods

• A variety of fruits and vegetables

• Whole grains

• Low fat dairy products

• Skinless poultry and fish

• Nuts and legumes

• Non-tropical vegetable oils

Eat less or avoid

• Saturated fats and trans-fat

• Beverages and foods with added sugar

• High sodium foods and salt

• Alcohol (with moderation)

Source: Adapted from AHA, Oct. 201649

Questions?

Elvira de Mejia

edemejia@illinois.edu

50

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CPEUs/Certificate of Completion

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52

Nutrition and Wellness

Upcoming Event

Evidence-based guidelines for the nutritional

management of adult oncology patients

• Date: Thursday, May 4, 2017

• Time: 11:00 am – 12:00 pm Eastern

• Location: https://learn.extension.org/events/3026

For more information on MFLN Nutrition and Wellness go to:

https://militaryfamilies.extension.org/nutrition-and-wellness

53

MFLN Intro

We invite MFLN Service Provider Partners

to our private LinkedIn Group!

https://www.linkedin.com/groups/8409844

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55This material is based upon work supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, and the Office of Military Family

Readiness Policy, U.S. Department of Defense under Award Number 2015-48770-24368.